1. Field of the Invention
The present invention relates to immunogenic peptides derived from human prostate cancer antigen (PSA-derived peptides) and their use as vaccines to treat or prevent prostate cancer. The invention is also related to dendritic cells from a patient having prostate cancer, which dendritic cells have been exposed to one or more PSA-derived peptides, and their use to treat or prevent prostate cancer in the patient. The invention is also directed to T-cells from a patient which cells are specific for PSA-activated peptide(s), and their uses to treat or prevent prostate cancer.
2. Description of the Related Art
Prostate cancer is the most common form of cancer among males, with an estimated incidence of 30% in men over the age of 50. Overwhelming clinical evidence shows that human prostate cancer has the propensity to metastasize to bone, and the disease appears to progress inevitably from androgen dependent to androgen refractory status, leading to increased patient mortality. This prevalent disease is currently the second leading cause of cancer death among men in the U.S. In 1996; 317,000 new cases of prostate adenocarcinoma were diagnosed and over 41,400 men died of the disease (Karp et al., 1996). Only lung cancer has a higher mortality. The chance of a man developing invasive prostate cancer during his lifetime is 1 in 6 or 15.4% at the age of 50; a man has a 42% chance of developing prostate cancer and 2.9% of dying from the disease. While advances in early diagnosis and treatment of locally confined tumors have been achieved, prostate cancer is incurable once it has metastasized. Unfortunately, patients with metastatic prostate cancer on hormonal therapy will eventually develop an androgen-refractory (androgen independent) state that will lead to disease progression and death. In spite of considerable research into therapies for the disease, prostate cancer remains difficult to treat. Commonly, treatment is based on surgery and/or radiation therapy, but these methods are ineffective in a significant percentage of cases. Two previously identified prostate specific proteins—prostate specific antigen (PSA) and prostatic acid phosphatase (PAP)—have thus far shown limited therapeutic and diagnostic potential. For example, PSA levels do not always correlate well with the presence of prostate cancer, being positive in a percentage of non-prostate cancer cases, including benign prostatic hyperplasia (BPH). Furthermore, PSA measurements correlate with prostate volume, and do not indicate the level of metastasis.
The PSA blood test has revolutionized the early diagnosis of prostate cancer and the effectiveness of treatment. PSA is a proteolytic enzyme in the family of serine proteases and one of the most abundant proteins in the prostate secretions. Current methods of treatment include radical prostatectomy, radiation, and hormonal suppression. To determine the appropriate method of treatment, factors such as the age of the patient and severity of the disease are often considered. The disease generally is more aggressive for younger patients. Any tumor greater than 0.5 cc is typically considered clinically significant. The preferred treatment for localized prostate cancer is radical prostatectomy. This treatment may result in death, incontinence, impotence, rectal injury, or pulmonary emboli.
In the last 15 years two sentinel insights in the immunotherapy of cancer have become clear; a) patients with cancer do, in fact, have an immune response to their tumor and, b) the target of the immune response in these patients are usually antigens derived from normal self proteins to which the cancer-bearing state has somehow released self tolerance. Hence, cancer reactivity is self reactivity, and the characteristics of a successful cancer immunotherapy will likely resemble autoimmunity. Specific immunotherapy of cancer has therefore consisted, for the most part, of the identification of and vaccination with such antigens by a variety of strategies in the hopes of augmenting the immune response to cancer antigens and bringing about a therapeutic effect. The development of immunotherapy for prostate cancer based on this model is in its infancy compared to other malignancies. Yet, prostate cancer is ideal for this approach because the disease is common, tends to be slowly progressive and any destruction of normal prostate tissue is of no apparent consequence.
Thus, it is desirable to provide improved methods of treatment for prostate cancer that reduce the likelihood of one or more of these unpleasant side effects. In particular, it is desirable to provide improved methods of treatment that reduce the likelihood of the treatment rendering the patient impotent. Finally, no effective treatment currently exists for patients with prostate cancer that has spread outside the prostate gland; these men have the highest risk of death for prostate cancer.